Study of ZG0895.HCl in Patients With Advanced Solid Tumors

NCT ID: NCT05877664

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-08
• Study Completion Date: 2026-06-30

Brief Summary

The primary objective of this study is to assess the tolerability and safety of ZG0895.HCl, and to assess the maximum tolerated dose (MTD)/ recommended phase 2 dose (RP2D) of ZG0895.HCl.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part1：Dose Escalation

During the dose-escalation stage, an accelerated titration design (ATD) will be utilized for the first three lower dose groups (0.06, 0.12 and 0.18 mg/m\^2). The conventional "3+3" dose escalation method will be used for the subsequent dose groups. The entire duration of 21 days after the first dose of ZG0895.HCl is defined as the dose-limiting toxicity (DLT) observation period.

Group Type: EXPERIMENTAL

ZG0895 Hydrochloride for Injection

Intervention Type: DRUG

The dose escalation of ZG0895.HCl is set as 0.06, 0.12, 0.18, 0.37, 0.75, 1.50, 2.25, 3.00, and 3.75 mg/m\^2 groups, subcutaneous (SC) injection once a week (QW)

Interventions

ZG0895 Hydrochloride for Injection

The dose escalation of ZG0895.HCl is set as 0.06, 0.12, 0.18, 0.37, 0.75, 1.50, 2.25, 3.00, and 3.75 mg/m\^2 groups, subcutaneous (SC) injection once a week (QW)

Intervention Type: DRUG

Other Intervention Names

ZG0895.HCl

Eligibility Criteria

Inclusion Criteria

• Fully understand the study and voluntarily sign the informed consent form(ICF).
• Age ≥ 18 and ≤ 75 years old at the time of signing the ICF, either male or female;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy ≥ 3 months.
• All adverse events from prior treatment have either returned to baseline or CTCAE 5.0 ≤ Grade 1(except for AEs not constituting a safety risk in the opinions of the investigators, e.g. alopecia, hypothyroidism which can be treated with a hormone replacement, etc).
• Both male and female participants (unless postmenopausal, surgical sterilization) and partners must agree to use a reliable form of contraception during the study treatment period and for at least 6 months after the last dose of the study drug.
• For lesions that have received radiation therapy, only after the progression of the lesions, they can be considered measurable lesions.

Part 1:

• Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1).
• Participants with histologically or cytologically confirmed diagnosis of advanced solid tumors, in whom available standard treatments failed or were intolerable.

Exclusion Criteria

• Participants receiving any of the following treatments:

1. Previously treated with systemic TLR7/8 immunomodulators.

2. Any other investigational product treatment within 4 weeks before the first dosing.

3. Chemotherapy, biotherapy, endocrine therapy (except for hormone replacement), and biological targeted medicines within 4 weeks before the first dosing. Local palliative radiotherapy, traditional Chinese medicine with anti-tumor effect, and small molecule targeted therapy within 2 weeks (or 5 half-lives, whichever is longer) before the first dosing.

4. Major surgery within 4 weeks before the first dosing for any reason (excluding puncture biopsy), or need to undergo elective surgery during the trial.

5. Potent CYP3A4/5 inducer or inhibitor within 2 weeks prior to administration of the first dose of the study drug.

6. Systemic immunosuppressive drugs within 2 weeks prior to administration of the first dose of the study drug, including systemic corticosteroids (>10 mg/day prednisone or equivalent).

7. Other immunomodulators within 2 weeks prior to administration of the first dose of the study drug, including but not limited to thymosin, interleukin-2 and interferon.

• Had CTCAE Grade ≥3 immune-related adverse events (irAE) after receiving immunotherapy.
• The main organ function meets any of the following criteria within 7 days prior to the first dosing. （Note: blood transfusion, EPO, G-CSF, albumin infusion and renal replacement therapy are not allowed within 14 days prior to treatment.)

1. Hematological function: ANC < 1.5×10^9/L, PLT < 75×10^9/L, Hemoglobin (Hb) < 100 g/L.

2. Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3×ULN; ALT and AST ≥ 5×ULN for participants with liver metastases; Total bilirubin (TBIL) ≥ 1.5×ULN; albumin < 30 g/L.

3. Creatinine clearance< 75 mL/min.

4. INR > 1.5 or APTT > 1.5×ULN.

5. The urine protein presents positive and the quantitative result of 24-h urine protein ≥ 1 g.

• Participants with symptomatic central nervous system (CNS) metastases or carcinomatous meningitis; or other evidence suggesting that the central nervous system metastasis or meningeal metastasis is not well-controlled and is judged by the investigator to be unsuitable for enrollment.
• Uncontrollable third cavity effusion (e.g. large amount pleural effusion, ascites, or pericardial effusion, etc.) requiring repeated drainage, which is judged by the investigator to be unsuitable for enrollment.
• Known history of neurological disorders affecting brain functional activities, including epilepsy or dementia.
• Severe cardiac-cerebral vascular disease, including but not limited to:

1. Acute myocardial infarction, unstable angina, stroke, or received coronary angioplasty or stent implantation within 6 months before the first dosing.

2. New York Heart Association functional class II to IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50% or the lower normal limit.

3. Uncontrollable hypertension (even though the best available treatment is used but systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg).

4. QTcF interval prolongation during the baseline period.

• Participants with active or history of autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for clinically stable autoimmune thyroid diseases.
• Active infection requiring systemic therapy within 7 days prior to the first dosing; active hepatitis B or hepatitis C, history of immunodeficiency virus (HIV) disease or HIV antibody positive.
• Priorly received allogeneic stem cell transplantation or solid organ transplantation.
• Known allergy to the ZG0895.HCl or any of its excipients; have severe allergy history (CTCAE Grade ≥ 3), such as severe urticaria, angioedema, severe anaphylaxis, etc.
• Females who are pregnant or nursing during the screening period.
• The investigators consider that the participants are not suitable to participate in the clinical study for other reasons.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Suzhou Zelgen Biopharmaceuticals Co.,Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jason Wu

Role: STUDY_CHAIR

Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Locations

Zhejiang Cancer Hospital

Zhejiang, Hangzhou, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenhao Cai

Role: CONTACT

caiwh@zelgen.com

+8615918725852

Facility Contacts

Ji Zhu

Role: primary

Other Identifiers

ZG0895-001

Identifier Type: -

Identifier Source: org_study_id